[unreadable] Postoperative, incisional pain is a unique but common form of acute pain. Since effective postoperative analgesia reduces morbidity following surgery, new treatments continue to be investigated. The proposal is dedicated toward studies of the mechanisms that subserve acute postoperative pain. It is through the study of mechanisms that a better understanding of incisional pain can be achieved and new treatments can be advanced. The work proposed will specifically characterize the mechanisms for incisional pain at the primary afferent nerve terminal. Neurophysiologic, biochemical, and molecular approaches will be used in concert to examine the mechanisms that contribute to activation and sensitization of nociceptive afferent fibers and subsequent primary hyperalgesia. Our working hypothesis is that 1) nociceptors responding to heat develop background activity and heat sensitization after incision. This sensitization is caused by H+ ions and NGF increased by the incision acting on VR1 receptors contributing to heat hyperalgesia and nonevoked pain behaviors. VR1 activation does not influence behaviors indicating mechanical hyperalgesia. 2) MIAs are activated by incision and develop mechanosensitivity. H+ ions and lactate increased by incision activate ASIC channels contributing to mechanical hyperalgesia. Incision-induced changes in expression of receptors activated by low pH will be measured. These data will determine the particular afferents sensitized by incision and the role of receptors activated by decreased tissue pH on pain behaviors caused by the incision. The proposed experiments will advance our understanding of postoperative incisional pain and provide a basis for rationale design of new pharmacologic treatment modalities. [unreadable] [unreadable]